Bladder Urothelial Carcinoma, Cholangiocarcinoma, Colorectal Cancer, Esophageal Cancer, Fallopian Tube Cancer, Gastric Cancer, Head and Neck Cancer, Hepatic Cancer, Non-small Cell Lung Cancer, Other Solid Tumors, Ovarian Cancer, Pancreatic Cancer, Primary Peritoneal Carcinoma, Renal Cell Carcinoma
Conditions
Keywords
LILRB2, CD85d, ILT-4, PD1, Bi-Specific, Immunotherapy, Solid tumor Malignancies, Dose escalation, Immunological
Brief summary
This is an open-label, non-randomized, multicenter, dose-escalation and expansion study in patients with selected solid tumors.
Detailed description
This study will determine the maximum tolerated dose of CDX-585 while also evaluating the safety, tolerability, and efficacy of CDX-585 in patients with cancer. Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-585. The dose-escalation part of the study will test the safety profile of CDX-585 and determine which dose of CDX-585 will be studied in the expansion portions of the study. All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur. The expansion portion of the study will further evaluate the safety of CDX-585 in selected tumor types at the dose level chosen during the escalation part of the study.
Interventions
DRUGCDX-585
CDX-585 is administered by infusion every 2 weeks
Sponsors
Celldex Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Recurrent, locally advanced, or metastatic solid tumor cancer excluding primary central nervous system tumors (e.g., glioblastoma). 2. Receipt of standard therapy for the tumor type in the recurrent, locally advanced, or metastatic setting. 3. Measurable (target) disease by iRECIST. 4. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 3 months following last treatment. 5. Willingness to undergo a pre-treatment and on-treatment biopsy, if required. Key
Exclusion criteria
1. History of severe hypersensitivity reactions to other monoclonal antibodies. 2. Previous treatment with any anti-ILT4 antibody. 3. Patients who have received more than 1 anti-PD-1 or anti-PD-L1 targeted therapy, including in the adjuvant setting. 4. Prior anti-PD-L1 based therapy within 12 weeks and prior anti-PD-1 based therapy within four weeks to the planned start of study treatment. 5. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers. For all other cancers, the patient must be disease-free for at least one year to be allowed to enroll. 6. Thrombotic events within the last six months prior to study treatment 7. Active, untreated central nervous system metastases. 8. Active autoimmune disease or documented history of autoimmune disease. 9. History of (non-infectious) pneumonitis or has current pneumonitis. There are additional criteria your study doctor will review with you to confirm eligibility.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose escalation: To determine the maximum tolerated dose of CDX-585 and to select the CDX-585 dose(s) for evaluation in tumor-specific expansion cohorts | Approximately 12 months | The rates of drug-related adverse events will be summarized, and maximum tolerated dose will be determined. |
| Tumor-specific expansion cohorts: To further evaluate the safety of CDX-585 by tumor type. | Approximately 6 months | The rates of drug-related adverse events will be summarized, and further evaluated in specific tumor types. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | Assessed up to approximately 1-3 years. | The percentage of patients who achieve best response of confirmed iCR or iPR, or immune stable disease (iSD) for at least four months |
| Duration of Response | First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years) | The interval from which measurement criteria are first met for iCR or iPR until the first date that progressive disease is objectively documented |
| Progression-free Survival | Cycle 1, day 1 to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years) | The time from start of study drug to time of progression or death, whichever occurs first |
| Safety and Tolerability of CDX-585 as assessed by CTCAE v5.0 | From first dose through 90 days after last dose | The rates of drug-related adverse events will be summarized and evaluated. |
| Pharmacokinetic Evaluation | Prior to, during, and at multiple time points after doses 1-4. Prior to every other dose from fifth dose, and at 30 and 90 days post last dose of study treatment | CDX-585 serum concentrations will be measured at specified visits |
| Immunogenicity Evaluation | Prior to the first three doses and every other dose from the fifth dose of study treatment, then 30 and 90 days after the last dose | Samples will be obtained for assessment of human anti-CDX-585 |
| Overall Survival | The time from start of study drug to death from any cause (up to approximately 1-3 years) | The time from start of study drug to death |
| Objective Response Rate | Assessed up to approximately 1-3 years. | The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR) |
Countries
United States
Outcome results
None listed